Healing wounds is a complex process of tissue repair and regeneration in response to injury. The healing response in skin wounds attempts to reconstitute a tissue similar to the original damaged one and this is accomplished via the concerted action of numerous skin cell types, collagens, cytokines, growth factors (GF s), chemokines, cell surface and adhesion molecules, as well as multiple extracellular matrix proteins. Autologous split-thickness skin grafting currently represents the most rapid, effective method of reconstructing large skin defects; however, in cases where a significant quantity of harvested graft is required, it represents yet another trauma to an already injured patient.
Some patent literature and academic literature is mentioned as follows, generally in roughly chronological order:
Wille, Jr., “Method for the formation of a histologically-complete skin substitute,” U.S. Pat. No. 5,292,655 issued Mar. 8, 1994;
Bernard, et al., “Process for creating a skin substitute and the resulting skin substitute,” U.S. Pat. No. 5,639,654 issued Jun. 17, 1997;
Bernard et al., “Skin substitute,” U.S. Pat. No. 5,667,961 issued Sep. 16, 1997;
Wille, Jr., “Serum free medium for use in the formation of a histologically complete living human skin substitute,” U.S. Pat. No. 5,686,307 issued Nov. 11, 1997;
Takai et al., “Wound healing composition using squid chitin and fish skin collagen,” U.S. Pat. No. 5,698,228 issued Dec. 16, 1997;
Wille, Jr., “Cell competency solution for use in the formation of a histologically-complete, living, human skin substitute,” U.S. Pat. No. 5,795,781 issued Aug. 18, 1998;
S. Hybbinette et al., “Enzymatic dissociation of keratinocytes from human skin biopsies for in vitro cell propagation,” Exp Dermatol., 1999: February; 8(1):30-8;
Mares-Guia, “Non-immunogenic, biocompatible macromolecular membrane compositions, and methods for making them,” U.S. Pat. No. 6,262,255 issued Jul. 17, 2001;
D. W. Hutmacher, “Scaffold design and fabrication technologies for engineering tissues—state of the art and future perspectives,” J. Biomater. Sci. Polymer Edn, 12:1, 107-124 (2001);
Conrad et al., “Skin substitutes and uses thereof,” US 20020164793 published Nov. 7, 2002;
Ramos et al., “Method for the preparation of immunologically inert amniotic membranes,” US 20040126878 published Jul. 1, 2004;
Conrad et al., “Skin substitutes and uses thereof,” U.S. Pat. No. 6,846,675 issued Jan. 25, 2005;
Conrad et al., “Skin substitutes and uses thereof,” US 20050226853 published Oct. 13, 2005;
S. G. Priya, et al., “Skin Tissue Engineering for Tissue Repair and Regeneration,” Tissue Engineering: Part B, 14:1, 2008, 105-118;
G. S. Schultz, et al., “Interactions between extracellular matrix and growth factors in wound healing,” Wound Rep Reg 17, 153-162 (2009);
Conrad et al., “Skin substitutes and uses thereof,” U.S. Pat. No. 7,541,188 issued Jun. 2, 2009;
Woodroof, “Laser-Perforated Skin Substitute,” US 20090230592 published Sep. 17, 2009;
Woodroof, et al., “Artificial Skin Substitute,” US 20090232878 published Sep. 17, 2009;
Woodroof; “Temporary Skin Substitute comprised of biological compounds of plant and animal origins,” US 20090234305 published Sep. 17, 2009;
Woodroof, et al., “Skin Substitute Manufacturing Method,” US 20100000676 published Jan. 7, 2010;
Woodroof, et al., “Artificial skin substitute,” U.S. Pat. No. 7,815,931 issued Oct. 19, 2010;
Mirua, et al., “Skin Substitute Membrane, Mold, and Method of Evaluating External Preparation for Skin,” US 20110098815 published Apr. 28, 2011;
Israelowitz et al., “Apparatus for the growth of artificial organic items, especially human or animal skin,” US 20110159582 published Jun. 30, 2011;
Guenou, “Methods for Preparing Human Skin Substitutes from Human Pluripotent Stem Cells,” US 20110165130 published Jul. 7, 2011;
Bush et al., “Bioengineered Skin Substitutes,” US 20110171180 published Jul. 14, 2011;
Yoo et al., “Delivery system,” US 20110172611 published Jul. 14, 2011;
M. V. Karaaltin et al., “Adipose Derived Regenerative Cell Therapy for Treating a Diabetic Wound: A Case Report,” Oct. 6, 2011;
Chernokalskaya, et al., “Polymeric Membranes with Human Skin-like Permeability Properties and uses thereof,” US 20110281771 published Nov. 17, 2011;
Miura et al., “Application method of external dermatological medications, evaluating method of the same, application evaluating apparatus, and application evaluating program,” US 20120022472 published Jan. 26, 2012;
D. Rosenblatt, “Researchers aim to ‘print’ human skin,” Feb. 15, 2011, www.cnn.com;
Miura et al., “Skin substitute membrane, mold, and method of evaluating external preparation for skin,” US 20120109300 published May 3, 2012;
R. Kirsner, et al., “Spray-applied cell therapy with human allogeneic fibroblasts and kertinocytes for the treatment of chronic venous leg ulcers: a phase 2, multicentre, double-blind, randomised, placebo-controlled trial,” www.thelancet.com, vol. 380, Sep. 15, 2012;
B. Raelin, “Wake Forest 3D Prints Skin Cells Onto Burn Wounds,” Jul. 19, 2012, www.3dprinter-world.com;
A. Lutz, “Printed Skin Cells Will Change How We Treat Burns Forever”, Aug. 3, 2012, www.businessinsider.com;
Miura et al., “Skin substitute membrane, mold, and method of evaluating external preparation for skin,” U.S. Pat. No. 8,337,554 issued Dec. 25, 2012;
“Printing Skin,” www.medicaldiscoverynews.com/shows/202_printSkin.html, undated;
C. M. Zelen, et al., “A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers,” International Wound Journal, ISSN 1742-4801, 2013;
H. Kim, et al., “Evaluation of an Amniotic Membrane-Collagen Dermal Substitute in the Management of Full-Thickness Skin Defects in a Pig,” Archives of Plastic Surgery, 2013, 40:1, 11-18;
“SkinPrint: 3D Bio-printed human skin can help burn victims”, May 16, 2013, www.3ders.org;
K. Maxey, “3D Printed, Transplantable Skin in 5 Years?”, May 17, 2013, www.engineering.com;
H. Briggs, “Artificial human ear grown in lab,” Jul. 31, 2013, www.bbc.co.uk;
S. Leckart, “How 3-D Printing Body Parts Will Revolutionize Medicine,” Aug. 6, 2013, www.popsci.com;
Thangapazham et al., “Hair follicle neogenesis,” US 20130209427 published Aug. 15, 20131
T. Lu et al., “Techniques for fabrication and construction of three-dimensional scaffolds for tissue engineering,” Internat'l Journal of Nanomedicine, 2013:8, 337-350.
Although there are a number of reports of skin autografts produced in vitro, they take weeks to generate—which is too long a waiting period for a patient whose wound needs treatment. Quicker production of skin autografts is an unmet need and unsolved problem.
In several studies conducted using amniotic membrane (AM) in both acute and chronic wounds, much of the first round placement is absorbed into the body. In some cases, it takes as many of 3-4 full grafts of AM in order to result in full closure of the wound. Less graft being absorbed into the body so that it is unable to contribute to closing the wound is an unsolved problem.
Another difficult unsolved problem has been that when an undamaged donor area of skin of a patient is harvested and used as an autograft for treating the patient's own wound, the donor site often becomes a non-healing wound.
There are complicated, unsolved problems and unmet needs for better technologies in wound grafting and wound healing.